title: Cholecystokinin octapeptide inhibits Ca2+-dependent amylase secretion from permeabilized pancreatic acini by blocking the MgATP-dependent priming of exocytosis.
abstract: At present little is known about how the low-affinity cholecystokinin receptor inhibits secretagogue-stimulated amylase secretion from pancreatic acinar cells. To examine this question we have determined how cholecystokinin octapeptide (CCK8) influences Ca2+-dependent amylase secretion from alpha-toxin-permeabilized pancreatic acini. CCK8 significantly inhibited Ca2+-stimulated amylase secretion. The inhibitory actions of CCK8 were completely blocked by the addition of JMV-180, a specific antagonist for the low-affinity CCK8 receptor. Previous studies have shown that Ca2+-dependent amylase secretion from alpha-toxin-permeabilized acini has two distinct phases [Padfield and Panesar (1997) Am. J. Physiol. 36, G655-660]. There is an initial rapid phase of secretion which represents release from exocytotic sites primed by MgATP prior to permeabilization. This is followed by a slower sustained phase of secretion which, in part, reflects the MgATP-dependent repriming of the exocytotic machinery. CCK8 did not influence the initial rapid phase of the Ca2+-dependent secretory response, but inhibited the second slower sustained phase. Moreover, CCK8 was shown to inhibit the MgATP-dependent priming of exocytosis in the acini. These results indicate that the low-affinity CCK receptor blocks stimulated amylase secretion by inhibiting the MgATP-dependent repriming of exocytosis.
authors.affiliation: Department of Pharmacological and Physiological Science, St. Louis University Health Sciences Center, 1402 South Grand Boulevard, St. Louis, MO 63104, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Padfield
authors.forename: N
authors.initials: N
authors.lastname: Panesar
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology*; D000681:Amylases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects*; D010179:Pancreas / Q000378:metabolism*; D010189:Pancreatic Juice / Q000201:enzymology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D051381:Rats; D012844:Sincalide / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D010738:Type C Phospholipases; D000681:Amylases; D012844:Sincalide; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium